Rational Chemical Modification of Adiponectin Variants

Abstract

An adiponectin variant with at least a 3-fold increased solubility relative to residues 110 - 244 of human adiponectin, wherein the adiponectin variant has at least one covalently attached non-peptide moiety at at least one position selected from the group consisting of: A108, Y109, S146, D179, E220, R221, and L224, relative to human adiponectin

1 . An adiponectin variant with at least a 3-fold increased solubility relative to residues 110-244 of SEQ ID NO: 1, wherein said adiponectin variant comprises at least one covalently attached PEG moiety at at least one residue selected from the group consisting of: A108C, Y109C, S146C, D179C, E220C, R221 C, and L224C, relative to human adiponectin (SEQ ID NO: 1).  
     
     
         2 . An adiponectin variant of  claim 1 , where said variant comprises at least one modification selected from the group consisting of: 122H, 122S, 125E, 125H, 125T, 184H, 207E, and 207K.  
     
     
         3 . An adiponectin variant with increased soluble expression, wherein said adiponectin variant comprises a covalently attached PEG moiety at a residue selected from the group consisting of: A108, Y109, S146, D179, E220, R221, and L224, relative to human adiponectin (SEQ ID NO:1), wherein said variant residue is a non-naturally occurring amino acid.  
     
     
         4 . An adiponectin variant with at least a 3-fold increased solubility relative to residues 110-244 of SEQ ID NO: 1, wherein said adiponectin variant comprises at least one covalently attached non-peptide moiety at at least one position selected from the group consisting of: A108, Y109, S146, D179, E220, R221, and L224, relative to human adiponectin (SEQ ID NO: 1).